ES2227500T3 - (s)-4-amino.5-cloro-2-metoxi-n-(1-(1-(2-tetrahidrofuril-carbonil)-4-piperidinilmetil)-4-piperidinil) benzamina para el tratamaiento de desordenes de la motilidad gastrointestinal. - Google Patents
(s)-4-amino.5-cloro-2-metoxi-n-(1-(1-(2-tetrahidrofuril-carbonil)-4-piperidinilmetil)-4-piperidinil) benzamina para el tratamaiento de desordenes de la motilidad gastrointestinal.Info
- Publication number
- ES2227500T3 ES2227500T3 ES03250050T ES03250050T ES2227500T3 ES 2227500 T3 ES2227500 T3 ES 2227500T3 ES 03250050 T ES03250050 T ES 03250050T ES 03250050 T ES03250050 T ES 03250050T ES 2227500 T3 ES2227500 T3 ES 2227500T3
- Authority
- ES
- Spain
- Prior art keywords
- compound
- amino
- chloro
- acid
- piperidinyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 238000011282 treatment Methods 0.000 title claims description 16
- 230000004899 motility Effects 0.000 title claims description 10
- 230000002496 gastric effect Effects 0.000 title description 16
- 229910052799 carbon Inorganic materials 0.000 title description 3
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 title description 2
- 239000002253 acid Substances 0.000 claims abstract description 56
- 150000003839 salts Chemical class 0.000 claims abstract description 29
- 150000001875 compounds Chemical class 0.000 claims description 160
- 238000002360 preparation method Methods 0.000 claims description 29
- 238000000034 method Methods 0.000 claims description 23
- 238000006243 chemical reaction Methods 0.000 claims description 21
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 20
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
- MMAHZLJRNLZQCI-NRFANRHFSA-N 4-amino-5-chloro-2-methoxy-n-[1-[[1-[(2s)-oxolane-2-carbonyl]piperidin-4-yl]methyl]piperidin-4-yl]benzamide Chemical compound COC1=CC(N)=C(Cl)C=C1C(=O)NC1CCN(CC2CCN(CC2)C(=O)[C@H]2OCCC2)CC1 MMAHZLJRNLZQCI-NRFANRHFSA-N 0.000 claims description 11
- 201000010099 disease Diseases 0.000 claims description 10
- 102100040385 5-hydroxytryptamine receptor 4 Human genes 0.000 claims description 9
- 101710150225 5-hydroxytryptamine receptor 4 Proteins 0.000 claims description 9
- UJJLJRQIPMGXEZ-BYPYZUCNSA-N (2s)-oxolane-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCO1 UJJLJRQIPMGXEZ-BYPYZUCNSA-N 0.000 claims description 8
- 229940079593 drug Drugs 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 239000000126 substance Substances 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 4
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 3
- 230000000638 stimulation Effects 0.000 claims description 3
- 230000007160 gastrointestinal dysfunction Effects 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims 1
- 230000007661 gastrointestinal function Effects 0.000 claims 1
- 229940127557 pharmaceutical product Drugs 0.000 claims 1
- -1 2-tetrahydrofurylcarbonyl Chemical group 0.000 abstract description 35
- 230000000694 effects Effects 0.000 description 50
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 48
- 238000012360 testing method Methods 0.000 description 23
- 239000000203 mixture Substances 0.000 description 22
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- 239000002904 solvent Substances 0.000 description 20
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 18
- 239000003623 enhancer Substances 0.000 description 18
- 230000013872 defecation Effects 0.000 description 17
- 230000005176 gastrointestinal motility Effects 0.000 description 15
- 230000003389 potentiating effect Effects 0.000 description 15
- 108091005482 5-HT4 receptors Proteins 0.000 description 14
- 239000000243 solution Substances 0.000 description 13
- DCSUBABJRXZOMT-RBBKRZOGSA-N 4-amino-5-chloro-N-[(3R,4S)-1-[3-(4-fluorophenoxy)propyl]-3-methoxy-4-piperidinyl]-2-methoxybenzamide Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(=CC(N)=C(Cl)C=2)OC)OC)N1CCCOC1=CC=C(F)C=C1 DCSUBABJRXZOMT-RBBKRZOGSA-N 0.000 description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- 229940125782 compound 2 Drugs 0.000 description 12
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 11
- 229960005132 cisapride Drugs 0.000 description 11
- DCSUBABJRXZOMT-UHFFFAOYSA-N cisapride Natural products C1CC(NC(=O)C=2C(=CC(N)=C(Cl)C=2)OC)C(OC)CN1CCCOC1=CC=C(F)C=C1 DCSUBABJRXZOMT-UHFFFAOYSA-N 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- 241000699670 Mus sp. Species 0.000 description 10
- 239000002585 base Substances 0.000 description 10
- 238000002474 experimental method Methods 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 150000008065 acid anhydrides Chemical class 0.000 description 9
- 102000005962 receptors Human genes 0.000 description 9
- 108020003175 receptors Proteins 0.000 description 9
- 230000002829 reductive effect Effects 0.000 description 9
- 206010010774 Constipation Diseases 0.000 description 8
- 125000000217 alkyl group Chemical group 0.000 description 8
- 239000013078 crystal Substances 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
- 239000012528 membrane Substances 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 238000011321 prophylaxis Methods 0.000 description 8
- 241000282472 Canis lupus familiaris Species 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 7
- 230000003287 optical effect Effects 0.000 description 7
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 208000018522 Gastrointestinal disease Diseases 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 230000027455 binding Effects 0.000 description 6
- 229960003638 dopamine Drugs 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 239000003446 ligand Substances 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- TTWJBBZEZQICBI-UHFFFAOYSA-N metoclopramide Chemical compound CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OC TTWJBBZEZQICBI-UHFFFAOYSA-N 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 230000000144 pharmacologic effect Effects 0.000 description 6
- 125000006239 protecting group Chemical group 0.000 description 6
- 241000416162 Astragalus gummifer Species 0.000 description 5
- 241000700198 Cavia Species 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 5
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 5
- 229920001615 Tragacanth Polymers 0.000 description 5
- 230000003042 antagnostic effect Effects 0.000 description 5
- 210000001072 colon Anatomy 0.000 description 5
- 238000007796 conventional method Methods 0.000 description 5
- 230000002708 enhancing effect Effects 0.000 description 5
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 5
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 229960004503 metoclopramide Drugs 0.000 description 5
- 239000002325 prokinetic agent Substances 0.000 description 5
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 5
- 239000000018 receptor agonist Substances 0.000 description 5
- 229940044601 receptor agonist Drugs 0.000 description 5
- 238000001525 receptor binding assay Methods 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- 235000010487 tragacanth Nutrition 0.000 description 5
- 239000000196 tragacanth Substances 0.000 description 5
- 229940116362 tragacanth Drugs 0.000 description 5
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 4
- 102000004980 Dopamine D2 Receptors Human genes 0.000 description 4
- 108090001111 Dopamine D2 Receptors Proteins 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 4
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 4
- 235000012239 silicon dioxide Nutrition 0.000 description 4
- 230000009870 specific binding Effects 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
- 241000700199 Cavia porcellus Species 0.000 description 3
- 229940126062 Compound A Drugs 0.000 description 3
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000000556 agonist Substances 0.000 description 3
- 150000008041 alkali metal carbonates Chemical class 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000008602 contraction Effects 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 125000001072 heteroaryl group Chemical group 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 238000007327 hydrogenolysis reaction Methods 0.000 description 3
- 238000002329 infrared spectrum Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 238000002483 medication Methods 0.000 description 3
- 210000000653 nervous system Anatomy 0.000 description 3
- 230000009871 nonspecific binding Effects 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- 206010000060 Abdominal distension Diseases 0.000 description 2
- 208000019901 Anxiety disease Diseases 0.000 description 2
- 102100020756 D(2) dopamine receptor Human genes 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 229940123603 Dopamine D2 receptor antagonist Drugs 0.000 description 2
- 102000015554 Dopamine receptor Human genes 0.000 description 2
- 108050004812 Dopamine receptor Proteins 0.000 description 2
- 208000007882 Gastritis Diseases 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 101000931901 Homo sapiens D(2) dopamine receptor Proteins 0.000 description 2
- 201000005081 Intestinal Pseudo-Obstruction Diseases 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 2
- 206010028813 Nausea Diseases 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 206010051482 Prostatomegaly Diseases 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 206010047700 Vomiting Diseases 0.000 description 2
- 240000008042 Zea mays Species 0.000 description 2
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 2
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- 125000005907 alkyl ester group Chemical group 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 208000022531 anorexia Diseases 0.000 description 2
- 230000036506 anxiety Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 229940125904 compound 1 Drugs 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- 235000005822 corn Nutrition 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- 206010061428 decreased appetite Diseases 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 239000000442 dopamine 2 receptor blocking agent Substances 0.000 description 2
- 208000000718 duodenal ulcer Diseases 0.000 description 2
- 206010013990 dysuria Diseases 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 201000005917 gastric ulcer Diseases 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 230000002650 habitual effect Effects 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 208000002551 irritable bowel syndrome Diseases 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- 229960005181 morphine Drugs 0.000 description 2
- 230000008693 nausea Effects 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000001012 protector Effects 0.000 description 2
- 230000000506 psychotropic effect Effects 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 201000000980 schizophrenia Diseases 0.000 description 2
- 229940076279 serotonin Drugs 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 230000002485 urinary effect Effects 0.000 description 2
- 208000014001 urinary system disease Diseases 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 230000008673 vomiting Effects 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- HVRCLXXJIQTXHC-UHFFFAOYSA-M 1-methylindole-3-carboxylate Chemical compound C1=CC=C2N(C)C=C(C([O-])=O)C2=C1 HVRCLXXJIQTXHC-UHFFFAOYSA-M 0.000 description 1
- MWAGUKZCDDRDCS-UHFFFAOYSA-N 1-nitro-4-(4-nitrophenoxy)benzene Chemical compound C1=CC([N+](=O)[O-])=CC=C1OC1=CC=C([N+]([O-])=O)C=C1 MWAGUKZCDDRDCS-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- CFMZSMGAMPBRBE-UHFFFAOYSA-N 2-hydroxyisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(O)C(=O)C2=C1 CFMZSMGAMPBRBE-UHFFFAOYSA-N 0.000 description 1
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- MMAHZLJRNLZQCI-UHFFFAOYSA-N 4-amino-5-chloro-2-methoxy-n-[1-[[1-(oxolane-2-carbonyl)piperidin-4-yl]methyl]piperidin-4-yl]benzamide Chemical compound COC1=CC(N)=C(Cl)C=C1C(=O)NC1CCN(CC2CCN(CC2)C(=O)C2OCCC2)CC1 MMAHZLJRNLZQCI-UHFFFAOYSA-N 0.000 description 1
- IMXPDEDLOYRKHB-UHFFFAOYSA-N 4-amino-5-chloro-2-methoxy-n-[1-[[1-(oxolane-3-carbonyl)piperidin-4-yl]methyl]piperidin-4-yl]benzamide Chemical compound COC1=CC(N)=C(Cl)C=C1C(=O)NC1CCN(CC2CCN(CC2)C(=O)C2COCC2)CC1 IMXPDEDLOYRKHB-UHFFFAOYSA-N 0.000 description 1
- MMAHZLJRNLZQCI-OAQYLSRUSA-N 4-amino-5-chloro-2-methoxy-n-[1-[[1-[(2r)-oxolane-2-carbonyl]piperidin-4-yl]methyl]piperidin-4-yl]benzamide Chemical compound COC1=CC(N)=C(Cl)C=C1C(=O)NC1CCN(CC2CCN(CC2)C(=O)[C@@H]2OCCC2)CC1 MMAHZLJRNLZQCI-OAQYLSRUSA-N 0.000 description 1
- DDIJUTUITTWXQU-UHFFFAOYSA-N 4-amino-5-chloro-n-[1-[[1-(furan-2-carbonyl)piperidin-4-yl]methyl]piperidin-4-yl]-2-methoxybenzamide Chemical compound COC1=CC(N)=C(Cl)C=C1C(=O)NC1CCN(CC2CCN(CC2)C(=O)C=2OC=CC=2)CC1 DDIJUTUITTWXQU-UHFFFAOYSA-N 0.000 description 1
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 1
- 239000005725 8-Hydroxyquinoline Substances 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 101000773908 Archaeoglobus fulgidus (strain ATCC 49558 / DSM 4304 / JCM 9628 / NBRC 100126 / VC-16) Acetate-CoA ligase [ADP-forming] II Proteins 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 208000017283 Bile Duct disease Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- GKQLYSROISKDLL-UHFFFAOYSA-N EEDQ Chemical compound C1=CC=C2N(C(=O)OCC)C(OCC)C=CC2=C1 GKQLYSROISKDLL-UHFFFAOYSA-N 0.000 description 1
- 206010015137 Eructation Diseases 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 102000014630 G protein-coupled serotonin receptor activity proteins Human genes 0.000 description 1
- MOZPSIXKYJUTKI-UHFFFAOYSA-N GR 113808 Chemical compound C12=CC=CC=C2N(C)C=C1C(=O)OCC1CCN(CCNS(C)(=O)=O)CC1 MOZPSIXKYJUTKI-UHFFFAOYSA-N 0.000 description 1
- 206010052105 Gastrointestinal hypomotility Diseases 0.000 description 1
- 208000017228 Gastrointestinal motility disease Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 206010021333 Ileus paralytic Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 239000004166 Lanolin Substances 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 208000026139 Memory disease Diseases 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 206010029333 Neurosis Diseases 0.000 description 1
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229920002873 Polyethylenimine Polymers 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 206010039710 Scleroderma Diseases 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 239000004809 Teflon Substances 0.000 description 1
- 229920006362 Teflon® Polymers 0.000 description 1
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
- MOZPSIXKYJUTKI-RLXJOQACSA-N [1-[2-(methanesulfonamido)ethyl]piperidin-4-yl]methyl 1-(tritritiomethyl)indole-3-carboxylate Chemical compound C12=CC=CC=C2N(C([3H])([3H])[3H])C=C1C(=O)OCC1CCN(CCNS(C)(=O)=O)CC1 MOZPSIXKYJUTKI-RLXJOQACSA-N 0.000 description 1
- FZHHVJNKANNVMK-UHFFFAOYSA-N [4-[(4-aminopiperidin-1-yl)methyl]piperidin-1-yl]-(oxolan-2-yl)methanone Chemical compound C1CC(N)CCN1CC1CCN(C(=O)C2OCCC2)CC1 FZHHVJNKANNVMK-UHFFFAOYSA-N 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 206010000059 abdominal discomfort Diseases 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 229910052788 barium Inorganic materials 0.000 description 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
- 208000027687 belching Diseases 0.000 description 1
- 239000000440 bentonite Substances 0.000 description 1
- 235000012216 bentonite Nutrition 0.000 description 1
- 229910000278 bentonite Inorganic materials 0.000 description 1
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
- 150000003936 benzamides Chemical class 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- FGPWOZTYXWEYIV-UHFFFAOYSA-N benzyl 4-[[4-[(2-methylpropan-2-yl)oxycarbonylamino]piperidin-1-yl]methyl]piperidine-1-carboxylate Chemical compound C1CC(NC(=O)OC(C)(C)C)CCN1CC1CCN(C(=O)OCC=2C=CC=CC=2)CC1 FGPWOZTYXWEYIV-UHFFFAOYSA-N 0.000 description 1
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 229920003123 carboxymethyl cellulose sodium Polymers 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 229940105329 carboxymethylcellulose Drugs 0.000 description 1
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 208000023652 chronic gastritis Diseases 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 208000010643 digestive system disease Diseases 0.000 description 1
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000002183 duodenal effect Effects 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 201000006549 dyspepsia Diseases 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000001839 endoscopy Methods 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 238000013110 gastrectomy Methods 0.000 description 1
- 208000021302 gastroesophageal reflux disease Diseases 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 208000024798 heartburn Diseases 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 239000000852 hydrogen donor Substances 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 239000001341 hydroxy propyl starch Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 235000013828 hydroxypropyl starch Nutrition 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
- 208000008384 ileus Diseases 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
- 229960000367 inositol Drugs 0.000 description 1
- 230000008991 intestinal motility Effects 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 231100000225 lethality Toxicity 0.000 description 1
- 210000003750 lower gastrointestinal tract Anatomy 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 229910000000 metal hydroxide Inorganic materials 0.000 description 1
- 150000004692 metal hydroxides Chemical class 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004118 muscle contraction Effects 0.000 description 1
- ZUSSTQCWRDLYJA-UHFFFAOYSA-N n-hydroxy-5-norbornene-2,3-dicarboximide Chemical compound C1=CC2CC1C1C2C(=O)N(O)C1=O ZUSSTQCWRDLYJA-UHFFFAOYSA-N 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 210000001577 neostriatum Anatomy 0.000 description 1
- 208000015238 neurotic disease Diseases 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- BOTREHHXSQGWTR-UHFFFAOYSA-N oxolane-3-carboxylic acid Chemical compound OC(=O)C1CCOC1 BOTREHHXSQGWTR-UHFFFAOYSA-N 0.000 description 1
- 229960003540 oxyquinoline Drugs 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 201000007620 paralytic ileus Diseases 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 208000000689 peptic esophagitis Diseases 0.000 description 1
- AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 229940068984 polyvinyl alcohol Drugs 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- MCJGNVYPOGVAJF-UHFFFAOYSA-N quinolin-8-ol Chemical compound C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-UHFFFAOYSA-N 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000001226 reprecipitation Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- DKGZKTPJOSAWFA-UHFFFAOYSA-N spiperone Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CCC2(C(NCN2C=2C=CC=CC=2)=O)CC1 DKGZKTPJOSAWFA-UHFFFAOYSA-N 0.000 description 1
- 229950001675 spiperone Drugs 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 210000003568 synaptosome Anatomy 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- KAQZZWSBZVORPS-UHFFFAOYSA-N tert-butyl n-[1-(piperidin-4-ylmethyl)piperidin-4-yl]carbamate Chemical compound C1CC(NC(=O)OC(C)(C)C)CCN1CC1CCNCC1 KAQZZWSBZVORPS-UHFFFAOYSA-N 0.000 description 1
- LLQQAGQCAICDLW-SFHVURJKSA-N tert-butyl n-[1-[[1-[(2s)-oxolane-2-carbonyl]piperidin-4-yl]methyl]piperidin-4-yl]carbamate Chemical compound C1CC(NC(=O)OC(C)(C)C)CCN1CC1CCN(C(=O)[C@H]2OCCC2)CC1 LLQQAGQCAICDLW-SFHVURJKSA-N 0.000 description 1
- UJJLJRQIPMGXEZ-UHFFFAOYSA-N tetrahydro-2-furoic acid Chemical compound OC(=O)C1CCCO1 UJJLJRQIPMGXEZ-UHFFFAOYSA-N 0.000 description 1
- UJJLJRQIPMGXEZ-SCSAIBSYSA-N tetrahydrofuran-2-carboxylic acid Chemical compound OC(=O)[C@H]1CCCO1 UJJLJRQIPMGXEZ-SCSAIBSYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 210000001635 urinary tract Anatomy 0.000 description 1
- 201000002327 urinary tract obstruction Diseases 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 208000009935 visceral pain Diseases 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nutrition Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2002141262 | 2002-05-16 | ||
JP2002141262 | 2002-05-16 |
Publications (1)
Publication Number | Publication Date |
---|---|
ES2227500T3 true ES2227500T3 (es) | 2005-04-01 |
Family
ID=29267809
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ES03250050T Expired - Lifetime ES2227500T3 (es) | 2002-05-16 | 2003-01-03 | (s)-4-amino.5-cloro-2-metoxi-n-(1-(1-(2-tetrahidrofuril-carbonil)-4-piperidinilmetil)-4-piperidinil) benzamina para el tratamaiento de desordenes de la motilidad gastrointestinal. |
Country Status (26)
Country | Link |
---|---|
US (1) | US6696468B2 (cs) |
EP (1) | EP1362857B1 (cs) |
JP (1) | JP3643107B2 (cs) |
KR (1) | KR20040107520A (cs) |
CN (1) | CN1653063A (cs) |
AR (1) | AR040021A1 (cs) |
AT (1) | ATE273304T1 (cs) |
AU (1) | AU2003230245A1 (cs) |
BR (1) | BR0309933A (cs) |
CA (1) | CA2483368A1 (cs) |
CZ (1) | CZ20041084A3 (cs) |
DE (1) | DE60300021T2 (cs) |
DK (1) | DK1362857T3 (cs) |
ES (1) | ES2227500T3 (cs) |
HU (1) | HUP0501016A2 (cs) |
IL (1) | IL165012A0 (cs) |
MX (1) | MXPA04011332A (cs) |
NO (1) | NO20045469L (cs) |
PL (1) | PL372724A1 (cs) |
PT (1) | PT1362857E (cs) |
RU (1) | RU2004136853A (cs) |
SK (1) | SK50192004A3 (cs) |
TR (1) | TR200403020T2 (cs) |
TW (1) | TW200400186A (cs) |
WO (1) | WO2003097638A1 (cs) |
ZA (1) | ZA200409053B (cs) |
Families Citing this family (25)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SE9904377D0 (sv) * | 1999-12-01 | 1999-12-01 | Astra Pharma Prod | Pharmaceutical combinations |
SE0200844D0 (sv) | 2002-03-19 | 2002-03-19 | Astrazeneca Ab | Chemical compounds |
SE0200843D0 (sv) | 2002-03-19 | 2002-03-19 | Astrazeneca Ab | Chemical compounds |
SE0300957D0 (sv) | 2003-04-01 | 2003-04-01 | Astrazeneca Ab | Chemical compounds |
TW200533348A (en) * | 2004-02-18 | 2005-10-16 | Theravance Inc | Indazole-carboxamide compounds as 5-ht4 receptor agonists |
US7728006B2 (en) * | 2004-04-07 | 2010-06-01 | Theravance, Inc. | Quinolinone-carboxamide compounds as 5-HT4 receptor agonists |
US8309575B2 (en) | 2004-04-07 | 2012-11-13 | Theravance, Inc. | Quinolinone-carboxamide compounds as 5-HT4 receptor agonists |
TWI351282B (en) * | 2004-04-07 | 2011-11-01 | Theravance Inc | Quinolinone-carboxamide compounds as 5-ht4 recepto |
DE602005014566D1 (de) * | 2004-11-05 | 2009-07-02 | Theravance Inc | Chinolinon-carboxamid-verbindungen |
WO2006052640A1 (en) * | 2004-11-05 | 2006-05-18 | Theravance, Inc. | 5-ht4 receptor agonist compounds |
NZ555180A (en) * | 2004-12-22 | 2010-09-30 | Theravance Inc | Indazole-carboxamide compounds useful as 5-HT4 receptor agonists |
CN101163701A (zh) * | 2005-03-02 | 2008-04-16 | 施万制药 | 作为5-ht4受体激动剂的喹啉酮化合物 |
MY147756A (en) | 2005-05-25 | 2013-01-15 | Theravance Inc | Benzimidazole-carboxamide compounds as 5-ht4 receptor agonists |
US7256294B2 (en) * | 2005-05-25 | 2007-08-14 | Theravance, Inc. | Crystalline form of a benzimidazole-carboxamide medicinal compound |
TW200722419A (en) * | 2005-05-27 | 2007-06-16 | Astrazeneca Ab | Chemical compounds |
WO2006126948A1 (en) * | 2005-05-27 | 2006-11-30 | Astrazeneca Ab | Piperidines for the treatment of chemokine mediated diseases |
ES2397418T3 (es) | 2005-07-21 | 2013-03-06 | Astrazeneca Ab | Derivados de piperidina |
GB0525068D0 (en) | 2005-12-08 | 2006-01-18 | Novartis Ag | Organic compounds |
TWI423967B (zh) * | 2008-02-21 | 2014-01-21 | Dainippon Sumitomo Pharma Co | 醯胺衍生物及含有其之醫藥組合物 |
US8349852B2 (en) | 2009-01-13 | 2013-01-08 | Novartis Ag | Quinazolinone derivatives useful as vanilloid antagonists |
EP2531510B1 (en) | 2010-02-01 | 2014-07-23 | Novartis AG | Pyrazolo[5,1b]oxazole derivatives as crf-1 receptor antagonists |
WO2011092293A2 (en) | 2010-02-01 | 2011-08-04 | Novartis Ag | Cyclohexyl amide derivatives as crf receptor antagonists |
WO2011095450A1 (en) | 2010-02-02 | 2011-08-11 | Novartis Ag | Cyclohexyl amide derivatives as crf receptor antagonists |
US8546416B2 (en) | 2011-05-27 | 2013-10-01 | Novartis Ag | 3-spirocyclic piperidine derivatives as ghrelin receptor agonists |
WO2013164790A1 (en) | 2012-05-03 | 2013-11-07 | Novartis Ag | L-malate salt of 2, 7 - diaza - spiro [4.5 ] dec- 7 - yle derivatives and crystalline forms thereof as ghrelin receptor agonists |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH111472A (ja) | 1996-04-30 | 1999-01-06 | Dainippon Pharmaceut Co Ltd | ベンズアミド誘導体及びそれを含有する医薬組成物 |
CN1118452C (zh) | 1998-04-28 | 2003-08-20 | 大日本制药株式会社 | 1-[(1-取代-4-哌啶基)甲基]-4-哌啶衍生物、其生产方法、含有该化合物的药物组合物和这些化合物的中间体 |
JP2000080081A (ja) | 1998-06-24 | 2000-03-21 | Dainippon Pharmaceut Co Ltd | 1―〔(1―置換―4―ピペリジニル)メチル〕―4―ピペリジン誘導体及びそれを含有する医薬組成物 |
JP2001122784A (ja) | 1999-10-27 | 2001-05-08 | Dainippon Pharmaceut Co Ltd | 1−[(1−置換−4−ピペリジニル)メチル]−4−ピペリジン誘導体からなる医薬 |
-
2002
- 2002-12-18 US US10/321,615 patent/US6696468B2/en not_active Expired - Fee Related
-
2003
- 2003-01-03 PT PT03250050T patent/PT1362857E/pt unknown
- 2003-01-03 ES ES03250050T patent/ES2227500T3/es not_active Expired - Lifetime
- 2003-01-03 DE DE60300021T patent/DE60300021T2/de not_active Expired - Fee Related
- 2003-01-03 EP EP03250050A patent/EP1362857B1/en not_active Expired - Lifetime
- 2003-01-03 DK DK03250050T patent/DK1362857T3/da active
- 2003-01-03 AT AT03250050T patent/ATE273304T1/de not_active IP Right Cessation
- 2003-05-08 TW TW092112525A patent/TW200400186A/zh unknown
- 2003-05-15 RU RU2004136853/04A patent/RU2004136853A/ru not_active Application Discontinuation
- 2003-05-15 TR TR2004/03020T patent/TR200403020T2/xx unknown
- 2003-05-15 SK SK5019-2004A patent/SK50192004A3/sk unknown
- 2003-05-15 BR BR0309933-4A patent/BR0309933A/pt not_active Application Discontinuation
- 2003-05-15 CN CNA03811089XA patent/CN1653063A/zh active Pending
- 2003-05-15 IL IL16501203A patent/IL165012A0/xx unknown
- 2003-05-15 CZ CZ20041084A patent/CZ20041084A3/cs unknown
- 2003-05-15 MX MXPA04011332A patent/MXPA04011332A/es unknown
- 2003-05-15 AU AU2003230245A patent/AU2003230245A1/en not_active Abandoned
- 2003-05-15 CA CA002483368A patent/CA2483368A1/en not_active Abandoned
- 2003-05-15 HU HU0501016A patent/HUP0501016A2/hu unknown
- 2003-05-15 KR KR10-2004-7018158A patent/KR20040107520A/ko not_active Withdrawn
- 2003-05-15 PL PL03372724A patent/PL372724A1/xx not_active Application Discontinuation
- 2003-05-15 AR ARP030101702A patent/AR040021A1/es unknown
- 2003-05-15 JP JP2003137413A patent/JP3643107B2/ja not_active Expired - Fee Related
- 2003-05-15 WO PCT/JP2003/006051 patent/WO2003097638A1/en not_active Application Discontinuation
-
2004
- 2004-11-09 ZA ZA200409035A patent/ZA200409053B/en unknown
- 2004-12-15 NO NO20045469A patent/NO20045469L/no unknown
Also Published As
Publication number | Publication date |
---|---|
DE60300021D1 (de) | 2004-09-16 |
TW200400186A (en) | 2004-01-01 |
BR0309933A (pt) | 2005-02-09 |
DK1362857T3 (da) | 2004-12-20 |
SK50192004A3 (sk) | 2005-04-01 |
MXPA04011332A (es) | 2005-02-14 |
US6696468B2 (en) | 2004-02-24 |
HK1060118A1 (en) | 2004-07-30 |
RU2004136853A (ru) | 2005-06-27 |
CN1653063A (zh) | 2005-08-10 |
PT1362857E (pt) | 2004-11-30 |
DE60300021T2 (de) | 2005-09-08 |
EP1362857B1 (en) | 2004-08-11 |
ZA200409053B (en) | 2005-07-12 |
HUP0501016A2 (en) | 2006-02-28 |
IL165012A0 (en) | 2005-12-18 |
EP1362857A1 (en) | 2003-11-19 |
TR200403020T2 (tr) | 2005-05-23 |
AU2003230245A1 (en) | 2003-12-02 |
WO2003097638A1 (en) | 2003-11-27 |
JP3643107B2 (ja) | 2005-04-27 |
CZ20041084A3 (cs) | 2005-02-16 |
KR20040107520A (ko) | 2004-12-20 |
CA2483368A1 (en) | 2003-11-27 |
JP2004043453A (ja) | 2004-02-12 |
AR040021A1 (es) | 2005-03-09 |
ATE273304T1 (de) | 2004-08-15 |
NO20045469L (no) | 2005-02-16 |
PL372724A1 (en) | 2005-07-25 |
US20030216433A1 (en) | 2003-11-20 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
ES2227500T3 (es) | (s)-4-amino.5-cloro-2-metoxi-n-(1-(1-(2-tetrahidrofuril-carbonil)-4-piperidinilmetil)-4-piperidinil) benzamina para el tratamaiento de desordenes de la motilidad gastrointestinal. | |
TWI313264B (en) | Triamide-substituted heterobicyclic compounds | |
ES2234248T3 (es) | Derivados de 1-(1-sustituido-4-piperidinil) metil)-4-piperidina, procedimiento de produccion de estos; composiciones medicinales que contienen estos compuestos e intermediarios de estos compuestos. | |
ES2209190T3 (es) | (+) -norcisaprida util para trastornos mediados por 5-ht3 y 5-ht4. | |
KR101586507B1 (ko) | 아미드 유도체 및 이를 함유하는 약학적 조성물 | |
PT855397E (pt) | (r)-5-bromo-n-(1-etil-4-metil-hexa-hidro-1h-1,4-diazepin-6-il)-2-metoxi-6-metilamino-3-piridinocarboxamida processo para a sua preparacao e composicao farmaceutica contendo o referido composto | |
JP2004277318A (ja) | 1−(1−置換カルボニル−4−ピペリジニルメチル)ピペリジン誘導体およびそれを含有する医薬組成物 | |
JP2004277319A (ja) | 1−(4−ピペリジニルメチル)ピペリジニルアミド誘導体およびそれを含有する医薬組成物 | |
JP2005082508A (ja) | 2−アルコキシ−6−アミノ−5−ハロゲノ−n−(1−置換−4−ピペリジニル)ピリジン−3−カルボキサミド誘導体およびそれを含有する医薬組成物 | |
JP2001122784A (ja) | 1−[(1−置換−4−ピペリジニル)メチル]−4−ピペリジン誘導体からなる医薬 | |
JP5156806B2 (ja) | アミド誘導体からなる医薬 | |
JP2000080081A (ja) | 1―〔(1―置換―4―ピペリジニル)メチル〕―4―ピペリジン誘導体及びそれを含有する医薬組成物 | |
JP3222051B2 (ja) | 6−メトキシ−1h−ベンゾトリアゾール−5−カルボキサミド誘導体 | |
HK1060118B (en) | (s)-4-amino-5-chloro-2-methoxy-n-[1-[1-(2-tetrahydrofuryl-carbonyl)-4-piperidinylmethyl]-4-piperidinyl]benzamide for treating gastrointestinal motility disorders | |
JP2005170933A (ja) | (s)−4−アミノ−5−クロロ−2−メトキシ−n−[1−[1−(2−テトラヒドロフリルカルボニル)−4−ピペリジニルメチル]−4−ピペリジニル]ベンズアミドからなる医薬 | |
BRPI0807799B1 (pt) | Derivados de 2-piperazin-1-il-3h-imidazo[4,5-b]piridina, composição farmacêutica que os compreende, seu processo de preparação e uso | |
HK1145837B (en) | Amide derivative and pharmaceutical composition containing the same |